Biological and clinical picture in Immune Thrombocytopenia (ITP) patients: prospective cross-sectional data on a single centre population

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by isolated thrombocytopenia (PLT < 100.000/mmc). Patients may be asymptomatic at presentation, or they may present with mild mucocutaneous to life threatening bleeding. Irrespectively of bleeding problems, patient with ITP often report fatigue and health-related impaired quality of life. The incidence of ITP ranges from 2 to 4 cases per 100.000 person-years and although some patients experience only one episode of thrombocytopenia followed by immediate remission, more than 70% of patient present persistent or chronic ITP. The pathophysiology of ITP is complex and remains incompletely understood. Traditionally anti-PLT autoantibodies are considered to have a key role in PLT premature destruction, but nowadays an increasing relevant role is quoted on breakdown in self-tolerance which drives to autoimmune cell-mediated and autoantibodies mediated processes, causing PLT destruction with different mechanisms, including inadequate PLT production by megakaryocytes impaired by T-cell and autoantibodies and abnormalities of T-cell, such as skewing of T helper (Th) cells towards type 1 helper (Th1) and type 17 helper phenotype and a reduction in numbers and function of regulatory T cells (Treg), which could enhance autoimmune process. Diagnosis remains a process of ruling out other causes of thrombocytopenia, as there is no diagnostic test for ITP; antiplatelet antibodies is detected only in 50% of ITP patients, with low specificity and sensitivity, therefore this test is note recommended in the diagnostic workup, which includes collection of medical and drug history, physical examination, blood smear, blood tests on biochemistry, viral and serology screen, haemolysis screen, haematinics, blood proteins and electrophoresis. Treatment is recommended in bleeding patients and below 30.000/mmc PLT count. Glucocorticoids (dexamethasone and prednisone) are recommended as first line treatment. In case of bleeding and/or PLT count < 10.000/mmc, IVIG is indicated in association with steroids, but unfortunately only 30 to 50% of adults have a sustained response after glucocorticoids are discontinued. Those patients who present persistent or chronic ITP, in order to guarantee a safe PLT count (>30.000/mmc) and to prevent bleeding, undergo second and subsequent line of treatment, with thrombopoietin-receptor agonists (TPO-RA), such as eltrombopag, romiplostim and avatrombopag, immunosuppressive agents such as Rituximab, azathioprine, mycophenolate mofetil, ciclosporin, fostamatinib (an oral spleen tyrosine kinase (Syk) inhibitor), or splenectomy which remains highly effective options inducing long-lasting remissions in 60 to 70% of patients. In the absence of biomarkers to guide the choice of medication, treatment is selected on other factors, including adverse effects, required speed of response, drug-to-drug interaction, patient and clinician preference, drug availability. Although not yet validated, role of biomarkers has been investigated for diagnosis, monitoring and treatment response prediction. This single centre prospective cross-sectional study aims to collect both clinical and biological information on ITP patient population in charge among Haematology department Genoa, San Martino Hospital. Biological data collection includes testing for cytokines, biochemical and immune markers among the ITP patient population. For each enrolled patient clinical data were collected and reported, including state of disease at time of assessment, type, number and timing of previous and/or ongoing treatments, patient quality of life perception, disease history. Data collected provided a biological picture at one-point time of a heterogeneous ITP patient population at different timepoints of their disease course, connecting information with clinical data (state of disease, type of previous or ongoing treatment and response, Quality of Life data). The main goal of this project was to collect a biological snapshot of ITP patients from this single centre population, providing synchronous clinical information in order to both compare results with the available published data and have a starting point for future longitudinal studies.